Methyl N-(2-amino-1,2-dicyanovinyl)formimidate, which is one type of the RMDs according to the first mode of the present invention, is a useful material of an intermediate for producing AICN which is a precursor of urazamide of a hepatoprotective drug, dacarbazine and temozoromide of antineoplastic drugs, or producing 4,5-dicyanoimidazole (hereinafter, referred to as DCI in some cases).
As a method for synthesizing RMD, Non-Patent Document 1 describes a method for synthesizing ethyl N-(2-amino-1,2-dicyanovinyl)formimidate (hereinafter, referred to as EMD in some cases) by reacting diaminomaleonitrile (hereinafter, referred to as DAMN in some cases) and triethyl orthoformate in dioxane at a high temperature.
In addition, Patent Document 1 discloses a method for producing an alkyl N-(2-amino-1,2-dicyanovinyl)formimidate characterized by reacting diaminomaleonitrile and a trialkyl orthoformate in an alcohol having 1 to 5 carbon atoms by means of heating and refluxing.
It is known that under high temperature conditions, DAMN is decomposed or a polymerization reaction occurs. Even in the aforementioned production methods, by-products are produced by side reactions of the aforementioned DAMN. In addition, RMDs are easily decomposed under high temperature conditions. For this reason, even if an RMD is produced in accordance with the aforementioned production method, a part of the RMD is decomposed. Therefore, development of a method in which RMD can be synthesized within a short period of time under low temperature conditions is desirable.
On the other hand, it is known that AICN or AICA which is an intermediate of medicine can be obtained by amidinating an RMD to form an N-(2-amino-1,2-dicyanovinyl)formamidine (hereinafter, referred to as AMD in some cases), subsequently carrying out a cyclization reaction and a hydrolysis reaction in a basic aqueous solution (for example, see Patent Document 2). Increasing the efficiencies of the aforementioned cyclization reaction and hydrolysis reaction and enhancing yield of AICN and AICA are desirable. A method for producing an RMD which is a raw material of AMD used in the aforementioned cyclization reaction may effect efficiency of the cyclization reaction or the like. For this reason, it is important that the method for producing the RMD complies with the cyclization reaction.

N-(2-amino-1,2-dicyanovinyl)formamidine of the second mode of the present invention is a useful raw material of an intermediate for producing DCI, AICN or AICA which is a precursor of urazamide of a hepatoprotective drug, or dacarbazine and temozoromide of antineoplastic drugs.
Examples of synthesis methods for AMD-H include a method in which AMD-His obtained by a one-step reaction from diaminomaleonitrile and a method in which AMD-His obtained by a two-step reaction from diaminomaleonitrile.
As the one-step synthesis method, for example, Non-Patent Document 1 discloses a method in which DAMN and formamidine acetate are heated to refluxing temperature in ethanol. However, the yield thereof is only 2%.
Patent Document 2 and Patent Document 3 disclose a method in which diaminomaleonitrile, hydrogen chloride, and isobutyronitrile or hydrogen cyanide are reacted in an organic solvent.
In addition, Patent Document 4 discloses a method in which diaminomaleonitrile, formamide and phosphorous oxychloride are reacted in a solvent such as tetrahydrofuran.
On the other hand, as the two-step synthesis method, for example, Non-Patent Document 2 discloses a method in which diaminomaleonitrile and triethyl orthoformate are reacted in dioxane at a high temperature to synthesize EMD, and EMD and ammonia are reacted in chloroform with aniline hydrochloride as a catalyst at a temperature of not more than −20° C.
In addition, Patent Document 1 discloses a method in which diaminomaleonitrile and a trialkyl orthoformate are heated and refluxed in an alcohol having 1 to 5 carbon atoms to synthesize an alkyl N-(2-amino-1,2-dicyanovinyl)formimidate, and the alkyl N-(2-amino-1,2-dicyanovinyl)formimidate is reacted with ammonia in an alcohol having 1 to 5 carbon atoms.
In addition, Patent Document 5 discloses, as examples of a method of producing AMD-H by reacting an RMD represented by a compound shown by the following formula (2-I) and ammonia, (1) a method in which an ammonia gas is blown into a solution or suspension of RMD in an alcohol having 1 to 5 carbon atoms, (2) a method in which an ammonia gas is blown into an alcohol having 1 to 5 carbon atoms to dissolve ammonia therein, followed by directly adding RMD thereto or adding a solution or suspension of RMD in an alcohol having 1 to 5 carbon atoms thereto, (3) a method in which a solution or suspension of RMD in an alcohol having 1 to 5 carbon atoms is added to ammonia condensed at a low temperature, (4) a method in which an aqueous ammonia is used instead of using the ammonia gas in the aforementioned method (1) or (2), and the like.

In formula (2-I), R11 is an optionally substituted alkyl group, or an optionally substituted aryl group.
On the other hand, it is known that AICN or AICA which is an intermediate of medicine can be obtained by amidinating RMD to obtain N-(2-amino-1,2-dicyanovinyl)formamidine, followed by subjecting to a cyclization reaction and a hydrolysis reaction in a basic aqueous solution (for example, see Patent Document 2). Increasing the efficiencies of the aforementioned cyclization reaction and hydrolysis reaction and enhancing the yields of AICN and AICA are desirable. A method for producing AMD-H used in the aforementioned cyclization reaction may effect efficiency of the cyclization reaction or the like. For this reason, it is important that the method for producing AMD-H complies with the cyclization reaction.

AICA or AICN which is one type of aminoimidazole derivatives represented by formula (3-V) according to the third mode of the present invention is a useful raw material of an intermediate for producing urazamide of a hepatoprotective drug, and dacarbazine and temozoromide of antineoplastic drugs.
As a synthesis method for the aminoimidazole derivatives represented by formula (3-V), for example, a method in which 4-nitroimidazole-5-carboxamide is subjected to a catalytic reduction, a method in which phenylazomalonamidine is subjected to a reductive ring closure, a method in which α-amino-α-cyanoacetamide is used as a raw material, a method in which a compound having a purine nucleus is decomposed, and the like are known. However, the aforementioned methods have drawbacks for industrial use in view of easy availability or easiness of operation.
A method is known in which 4,5-dicyanoimidazole is synthesized from DAMN easily available as an industrial raw material (Japanese Examined Patent Application, Second Publication No. S46-4373), followed by hydrolyzing the compound (Japanese Examined Patent Application, Second Publication No. S41-21026) to synthesize 5-cyano-1H-imidazole-4-carboxamide, and the obtained compound is subjected to a Hofmann rearrangement reaction to convert into 5-amino-1H-imidazole-4-carbonitrile, followed by hydrolyzing the obtained compound to synthesize 5-amino-1H-imidazole-4-carboxamide. However, in the aforementioned synthesis method, yield is low.
Non-Patent Document 1 reports that AICN can be synthesized by ring-closing N-(2-amino-1,2-dicyanovinyl)formamidine. In addition, Non-Patent Document 2 and Non-Patent Document 3 report that a 1-substituted-5-aminoimidazole-4-carbonitrile can be synthesized by ring-closing an N-(2-amino-1,2-dicyanovinyl)-N′-substituted-formamidine.
Patent Document 3 and Patent Document 2 disclose that diaminomaleonitrile, hydrogen chloride, and isobutyronitrile or hydrogen cyanide are reacted in an organic solvent to obtain AMD, and the AMD is subjected to a cyclization reaction in an aqueous solution of sodium hydroxide to synthesize AICN or AICA. In addition, Patent Document 4 discloses that diaminomaleonitrile, formamide and phosphorous oxychloride are reacted in a solvent such as tetrahydrofuran to obtain AMD, and an aqueous solution or aqueous suspension of the obtained AMD is reacted with a basic compound to synthesize AICN. In addition, Patent Document 6 discloses a method in which AMD is cyclized and hydrolyzed in a basic aqueous solution to synthesize AICA.
Patent Document 1: Japanese Unexamined Patent Application, First Publication No. 2001-302609
Patent Document 2: WO 2004/035529
Patent Document 3: Japanese Unexamined Patent Application, First Publication No. 2001-158776
Patent Document 4: Japanese Unexamined Patent Application, First Publication No. 2002-155059
Patent Document 5: WO 2001/21592
Patent Document 6: Japanese Unexamined Patent Application, First Publication No. 2001-151760
Non-Patent Document 1: B. L. Booth et al., J. Chem. Soc. Perkin Trans. I, 1990, 1705
Non-Patent Document 2: B. L. Booth et al., J. Chem. Soc. Perkin Trans. I, 1992, 2120
Non-Patent Document 3: B. L. Booth et al., J. Chem. Soc. Perkin Trans. I, 1995, 669